tbuckley/cabot-search huggingface dataset:
Women with pathogenic variants in moderate penetrance breast cancer genes: How frequently do they meet high penetrance genetic testing criteria?
Authors: Nicole Casasanta, Emily R. Soper, Noura S. Abul-Husn
Journal: Journal of Clinical Oncology (2023)

10584 Background: 5-10% of breast cancers are associated with germline pathogenic variants in breast cancer predisposition genes. 2-5% of these variants are in moderate penetrance (MP) genes, conferring a relative risk to develop breast cancer of 2-5. Various personal history (PH) and family history (FH)-based criteria for testing high penetrance genes, such as BRCA1 and BRCA2, have been proposed, but it is unknown to what extent women with pathogenic variants in MP genes may meet such criteria. We evaluated PH and FH of cancer among women with pathogenic variants in MP genes in a diverse and unselected patient cohort in New York City to determine how often they met well-established genetic testing criteria from the National Comprehensive Cancer Network (NCCN). Methods: Exome sequence data from ~16,000 female Bio Me Biobank participants were evaluated for expected pathogenic (per ClinVar, or predicted loss-of-function) variants in ATM, BARD1, BRIP1, CHEK2, NF1, PALB2, RAD51C, and RAD51D. We extracted demographic information, PH and FH of breast, ovarian, and/or pancreatic cancer, and PH and FH of genetic testing from participant questionnaires and electronic medical record review. We then determined which participants met current NCCN criteria (version 1.2023) for high penetrance breast, ovarian, and pancreatic cancer genetic testing. Results: We identified 252 women with expected pathogenic variants in MP genes: 105 CHEK2, 58 ATM, 35 BRIP1, 24 PALB2, 9 BARD1, 8 NF1, 8 RAD51D, and 5 RAD51C. 30% met NCCN criteria, including 30% of those with CHEK2 variants, 36% ATM, 14% BRIP1, 33% PALB2, and 30% with variants in BARD1, NF1, RAD51D, or RAD51C. 36% of those who met NCCN criteria had previously undergone clinical genetic testing. 29 of 33 (88%) women with a PH of breast cancer and 52 of 81 (64%) women with a FH of breast cancer met criteria. Conclusions: Current genetic testing criteria focus on identifying individuals harboring pathogenic variants in high penetrance cancer genes. However, in our study, a substantial portion of women with a pathogenic variant in a MP breast cancer gene also met such criteria, particularly when PH or FH of breast cancer were present. Only a third of those who met NCCN criteria had undergone clinical genetic testing. These findings suggest that the majority of women with genetic risk for breast cancer may be missed in clinical practice. Studies have shown that most physicians would change management strategies for patients with pathogenic variants, including variants in MP genes. As our understanding of genetic risk for breast cancer continues to evolve, we must explore strategies to improve identification and management of individuals with variants in MP breast cancer genes.
Elevated cancer risk among individuals with combinations of cancer-related risk factors: A large claims database analysis.
Authors: Ze Cong, Xiangyang Ye, Allison W. Kurian
Journal: Journal of Clinical Oncology (2023)

10561 Background: Besides age, many risk factors have been associated with elevated cancer risk. Understanding cancer incidence rates among patients with single or multiple risk factors can help inform cancer prevention and detection efforts. Methods: A retrospective observational analysis was conducted on individuals aged 50-79 in 2020 using Optum’s de-identified Clinformatics Data Mart Database which includes Medicare Advantage (MA) (vast majority aged 65+) and commercially insured members (mostly below 65 and employed). Patients with no prior cancer diagnosis (continuously enrolled with no cancer claims for one year) and with cancer risk factors were identified using ICD-10-CM and CPT-4 codes, including autoimmune-related chronic inflammation (diabetes, inflammatory bowel disease, asthma, or rheumatoid arthritis) (INFLAM AUTO); non-autoimmune related chronic inflammation (fatty liver disease, obesity, or cirrhosis/chronic hepatitis B/C) (INFLAM NONAUTO); immunodeficiency (primary or secondary immunodeficiency, HIV, or status post organ transplant); and smoking. Cancer incidence rate ratios (IRR) were calculated by comparing one-year cancer incidence rate among the groups with risk factors versus the general population by insurance type (IRR&gt;1 means elevated risk of cancer). Groups with evidence of any risk factor and combinations of risk factors were assessed. Statistical significance of IRRs was evaluated using logistic regression models adjusting for demographic characteristics. Results: Cancer incidence rates of 1.12% and 2.11% were observed among the approximately 1.3 and 2.4 million general population aged 50-79 in commercial and MA plans, respectively. Enrollees with any of the risk factors or combinations analyzed had statistically significantly elevated risk of cancer (IRRs&gt;1.00, p&lt;0.05). Commercially insured groups with highest risk included transplant (IRR=7.68, prevalence=0.02%), immunodeficient and smokers (IRR=3.66, prevalence=0.16%), cirrhosis/chronic hepatitis B/C (IRR=2.61, prevalence=0.41%), INFLAM AUTO and smokers (IRR=2.43, prevalence=3.56%), and smoker (IRR=2.33, prevalence=11.11%). Results in MA were generally consistent with the commercial plan (Table). Conclusions: Patients in both commercial and MA plans with any risk factor experienced significantly elevated cancer risk. Cancer prevention and screening strategies can be informed by risk levels among different patient subgroups to optimize resource allocation. [Table: see text]
Inclusive innovation: World health organization (WHO) task-shifting principles in community health workers living with disabilities through women’s cancer screening in the EMPOWER Program.
Authors: Catherine Kanari, Dorothy Ogada Nyongo, Jacqueline Wambua, Raymond Muhanji
Journal: Journal of Clinical Oncology (2023)

e22512 Background: The W.H.O estimates that people with disabilities make up 15% of the world’s population. In the Horn of Africa (Djibouti, Kenya, Ethiopia &amp; Uganda) there have been several disability inclusion programs in Education, livelihoods and empowerment through the Development Response to Displacement Impacts Project (DRDIP). In Kenya, the Government has continued to leverage on the private sector to accelerate progress towards inclusion. A strategic partnership with Safaricom enabled provision of Assistive devices and medical cover exceptional approval to a tune of USD 223,000 to Persons with Disabilities in the formal and informal economy in Kenya. Women CHVs were selected to reduce cultural barriers because many women in the communities are more comfortable being screened by a fellow woman. Objectives: To identify and deploy women living with disabilities as community health volunteers in the county EMPOWER Clinics; To build capacity of women living with disabilities and enable them to accurately screen for breast and cervical cancer. Methods: A total of 25 women living with disabilities and 7 able-bodied women from Meru and Kisumu counties were selected for the training program through county disability coordinators. The training program consisted of a basic community health volunteer (CHV) module and focused on Breast and cervical cancer awareness topics. The CHVs were equipped with mobile phones with assistive technology (AT) features such as braille keyboards, magnifiers, and text-to-speech technology. The training was delivered through Amref Health Innovations' (AHI) LEAP platform in collaboration with 5 county community health assistants. The CHVs' understanding of the material was evaluated through performance tracking on the LEAP platform. The CHVs were also given regular feedback on their progress, and any areas of difficulty were addressed through additional support and guidance. Results: The trained CHVs demonstrated an increased understanding of breast and cervical cancer screening, as well as the skills necessary to perform medical tactile breast exams. The trained CHVs were then commissioned to be integrated into the community health workforce, with a focus on breast and cervical cancer screening and awareness. Conclusions: The deployment of inclusion-centered learning for women Community Health Volunteers (CHVs) living with disabilities is a promising approach for improving access to health services for this marginalized group. This program provides a model for promoting disability inclusion in health services and underscores the need for continued investment in disability-inclusive programs. The findings of this program can inform the development of similar programs in other regions and contribute to the achievement of universal health coverage and health for all.
Clinical characteristics, markers of adverse prognosis, and predictors of development of extramedullary multiple myeloma.
Authors: Saurabh Zanwar, Matthew Ho, Prashant Kapoor, Moritz Binder, Francis Buadi, Angela Dispenzieri, David Dingli, Amie L. Fonder, Morie A. Gertz, Wilson I. Gonsalves, Suzanne R. Hayman, Yi Lisa Hwa, Miriam A. Hobbs, Taxiarchis Kourelis, Martha Lacy, Nelson Leung, Eli Muchtar, Rahma M. Warsame, S. Vincent Rajkumar, Shaji Kumar
Journal: Journal of Clinical Oncology (2023)

8043 Background: Extramedullary Multiple Myeloma (EMM) has an aggressive clinical course and can present at diagnosis [primary EMM, (pEMM)] or relapse [secondary EMM, (sEMM)]. Here, we report clinical characteristics and outcomes of EMM, and predictive factors for the development of sEMM. Methods: We identified 299 patients with biopsy-proven EMM between 01/01/2000 and 12/31/2021. Patients with solitary plasmacytomas, paraskeletal MM and primary plasma cell leukemia were excluded. A 1:1 matched pair analysis (matched for year of diagnosis of MM for comparable follow-up and treatment eras) was performed to compare clinical characteristics and outcomes for patients with and without sEMM. Results: The median follow-up from the diagnosis of MM was 11.5 years (95%CI: 9.3-14.8). Of 299 patients, 204 (68%) patients had sEMM and 95 (32%) had pEMM, with largely comparable baseline characteristics (Table). The median overall survival (OS) from the diagnosis of sEMM was 0.7 (95% CI: 0.6-0.9) years compared to 3.6 (95%CI: 2.4-5.6) years for pEMM (p&lt;0.0001). For sEMM, mutlvariable analysis (MVA) for OS identified visceral organ involvement (eg. liver, lung/pleura, brain, pancreas, etc.) to be associated with inferior OS [HR 1.6 (95% CI: 1.1-2.4), p=0.01]; high-risk cytogenetics (HR-CTG), ISS-3 stage, and age did not impact OS from sEMM. For pEMM, HR-CTG [HR 2.3 (95% CI 1.1 -4.8), p=0.03] and ISS-3 stage [HR 3.1 (95% CI 1.5-6.7), p=0.003] were associated with inferior OS on MVA whereas visceral EMM or age did not impact OS from pEMM. On univariate analysis, patients with sEMM were younger (median age 58.7 vs 61 years, p=0.006), had a higher proportion of 1q duplication (32% vs 17%, p=0.001), t(4;14) [16% vs 9%, p=0.047] and elevated LDH (30% vs 19%, p=0.04), compared to the matched cohort of patients without sEMM. On MVA, younger age at diagnosis, t(4;14) and 1q duplication at diagnosis of MM were independent predictors of development of sEMM. The median OS from diagnosis of MM was 5.4 years (95%CI: 4.1-6.2) for patients with sEMM versus 7.5 years (95% CI: 6.4-10.1; p &lt;0.001) for the matched cohort. Secondary EMM was an independent poor prognostic marker for OS from the diagnosis of MM [HR 1.6 (95%CI: 1.2-2.1); p=0.004] in addition to age, ISS3 disease and HR-CTG. Conclusions: Outcomes of patients with EMM, especially sEMM, remain dismal. Patients with sEMM have higher rates of 1q duplication and t(4;14) at diagnosis of MM and carried an independent adverse prognosis in a matched cohort. [Table: see text]
Cost-utility of geriatric assessment in older adults with cancer: Results from the 5C trial.
Authors: Yeva Sahakyan, Qixuan Li, Lusine Abrahamyan, Martine Puts, Sarah Brennenstuhl, Mohammed Rashidul Anwar, Shant Yeretzian, Emma Matosyan, Bianca Mclean, Fay Strohschein, Aria Wills, George Tomlinson, Shabbir M.H. Alibhai
Journal: Journal of Clinical Oncology (2023)

12012 Background: Geriatric assessment is a guideline-recommended approach to optimize cancer management in older adults. We conducted a cost-utility analysis alongside the recently published 5C randomized controlled trial to compare geriatric assessment and management (GAM) with usual care in older adults with cancer. Methods: The economic evaluation was conducted from a societal perspective, using a 12-month time horizon. The 5C study enrolled patients age 65+ from 8 Canadian hospitals and randomly assigned them to receive GAM or usual care. Patients were initiating systemic therapy with curative or palliative intent. Quality-adjusted life years (QALYs) were measured using the EQ-5D-5L questionnaire. Healthcare utilization was evaluated using cost diaries and chart reviews. The primary outcome, an incremental monetary benefit (INMB), was evaluated for the full sample and for preselected subgroups. Multiple imputation was used to account for missing data. The 95% confidence intervals (CI) were computed using bootstrapping. Results: The study included 350 patients, of which 173 received GAM and 177 received usual care. At 12 months, the average QALYs per patient were 0.747 and 0.753 for GAM and usual care respectively (ΔQALY = -0.006, 95%CI: -0.06 to 0.05). The total average costs per patient were $48,397 and $45,342 for GAM and usual care (ΔCost = $3,078 (95% CI: -$5,336 to $12,050). At a cost-effectiveness threshold of $50,000/QALY the INMB was negative (-$3,962; 95% CI: -$7,117 to -$794) meaning that GAM was not cost-effective compared to usual care. In a subgroup analysis the INMB was positive ($4,639, 95% CI: $61 to $8,607) for patients treated with curative intent, and the intervention was cost effective in 78% of simulations, but remained negative (i.e. not cost-effective) for patients treated with palliative intent (INMB -$13,307, 95% CI -$18,063 to -$8,264). Conclusions: This is the first cost-utility analysis of GAM in cancer. The findings showed that GAM was cost-effective for cancer patients treated with curative intent but not for patients with palliative intent. Although the primary results of the 5C trial were negative, extrapolating our costing data to positive GAM trials like GAIN, GAP70, and INTEGERATE will provide a more complete picture of the cost effectiveness of GAM in this setting. Clinical trial information: NCT03154671 .
Spread through air spaces in non-small cell lung cancer: Experience of a tertiary hospital.
Authors: Virginia Calvo, Yago Garitaonaindia, Marta Martinez Cutillas, CRISTINA TRASEIRA, Isabel Redondo, Ramon Aguado, Ana Collazo Lorduy, Jose Luis Campo Cañaveral, Javier Martin Lopez, Aylen Vanessa Ospina Serrano, Mariola Blanco, Silvana Crowley, Alejandra Romero Roman, Mariana Gil Barturen, Consuelo Parejo, Mariano Provencio-Pulla
Journal: Journal of Clinical Oncology (2023)

e20606 Background: Tumor spread through air space (STAS) is a novel pattern of invasion related to poor prognosis in non-small cell cancer (NSCLC). In 2015, Kyuichi Kadota first described spread through air spaces (STAS) as a novel histologic pattern of invasion related to poor prognosis NSCLC. The objective of this study is to describe the incidence of STAS in a surgical series of NSCLC patients resected in Hospital Universitario Puerta de Hierro-Majadahonda and identify the association of STAS with clinicopathological characteristics. Methods: Observational retrospective cohort study was performed from 2015 to 2021. Inclusion criteria were: age more than 18 years, histologically confirmed diagnosis of NSCLC, clinical stage I-IV and radical treatment with surgery. Descriptive analysis was performed. Results: 178 patients were included. 69.1% (123) were male, median age was 68.0 years. In relation to histological subtypes: 65.2% were adenocarcinoma, 22.5% squamous-cell carcinoma and 12.3% other histologies. Patients were classified by pathological stage: 71.9% were in stage I, 11.4% in stage II, 15.6% in stage III and 1.1% in stage IV. STAS was observed in the surgical specimen in 62 cases (34.8%). In Table-1 the association of STAS with clinicopathological characteristics is shown. Conclusions: In our study, we found statistically significant association between STAS and histological subtype and presence of lympho-vascular invasion. STAS were present more frequently in adenocarcinoma and were associated with more incidence of lympho-vascular invasion, as reported in other studies. More analysis are required for further description of this dissemination pattern and its implication in the prognosis of the patients. [Table: see text]
Immunotherapy combined with rh-endostatin improved clinical outcomes over ICIs plus chemotherapy for second-line treatment of advanced NSCLC.
Authors: Hongxiang Huang, Peiyuan Zhong
Journal: Journal of Clinical Oncology (2023)

e21133 Background: Despite the fact that numerous clinical and preclinical studies have demonstrated the synergistic effects of combining antiangiogenic or chemotherapy with immunotherapy, no data have been found to indicate that combination therapy is more effective and safer as second-line therapy. Methods: We retrospectively compared the effectiveness and safety of ICIs plus rh-endostatin to ICIs plus chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). The evaluation indicators were progression-free survival (PFS), safety profile, overall response rate (ORR), disease control rate (DCR) and 1-year survival rate. Results: The median PFS with immunotherapy plus rh-endostatin (IE) was 7.10 months (95% CI, 4.64 to 9.56) versus 5.13 months (95% CI, 4.29 to 5.97) with immunotherapy plus chemotherapy (IC) (HR, 0.56; 95%CI, 0.33 to 0.95). Treatment-related adverse events of grade 3 or 4 occurred in 7.5% of the IE group versus 25.0% of the IC group. The ORR in the IE group was 35.0% versus 20.8% in the IC group ( P = 0.137), and the DCR in the IE group was 92.5% versus 77.1% in the IC group ( P = 0.049). The 1-year survival rate for the IE group was 69.4%, which was higher than the IC group's rate of 61.4%. Conclusions: Our study demonstrates that ICIs in conjunction with endostatin therapy, demonstrate high efficacy and safety, suggesting that such a combination of therapy may be a viable treatment option for pretreated NSCLC patients in the future.
The effect of ctDNA tumor fraction (TF) on overall survival and concordance between tissue genomics and ctDNA in Lung-MAP.
Authors: Philip C. Mack, Mary Weber Redman, David E. Kozono, Sam Callis, Hanna Tukachinsky, Khaled A. Tolba, Joel W. Neal, Saiama Naheed Waqar, Konstantin H. Dragnev, Charu Aggarwal, Fred R. Hirsch, Jyoti D. Patel, Roy S. Herbst, Anne C. Chiang, Karen L. Reckamp, Karen Kelly, Hossein Borghaei, Jhanelle Elaine Gray, David R. Gandara
Journal: Journal of Clinical Oncology (2023)

9035 Background: Discordance in genomic profiling between tumor tissue and ctDNA can occur due to inter-patient variability in shed tumor DNA, and intra-patient variability in sources of cell-free DNA (tumor heterogeneity, metastatic variants, CHIP). TF is an aneuploidy-based estimation of tumor-specific DNA in circulation. We evaluated the impact of TF levels on overall survival (OS), mutation concordance and tumor mutation burden in tissue (tTMB) and ctDNA (bTMB) in the LUNGMAP screening study. Methods: Eligible advanced NSCLC pts had blood drawn ≤30 days of fresh tissue biopsy with no intervening therapies. Genomic profiling was done by FoundationOne CDx and FoundationOne Liquid CDx. ctDNA TF was quantified via aneuploidy using deviations in genome-wide SNP coverage or somatic allele frequencies if under aneuploidy LoD. High TF was defined as ≥10%. Concordance among driver genes, cancer genes of interest (CGoI: T P53, PIK3CA, STK11, KEAP1, RB1, PTEN, ATM, BRCA1/2), and variant subtype were assessed by the percentage positive agreement (PPA) and positive predictive value (PPV) with 95% confidence intervals (CI). OS by TF used a Cox model and log-rank test. PPA and TF among CGoIs was compared with a Wilcoxon test. Correlation between tTMB and bTMB used Lin’s coefficient (LC). Results: 167 pts met inclusion criteria; 161 had TF data with 51 (32%) ≥10% (high TF). High TF was associated with worse OS (HR: 2.06 [1.43-2.95], p&lt;0.001). The PPA and PPV ranged from 50%-100% and 60%-100%, respectively for driver genes. The PPA was numerically larger for high versus low TF for most drivers (p=0.18) and significantly larger for all mutations and SNVs combined (Table). For CGoI, the distribution of PPA differed between high and low TF (p=0.03). The median PPA for CGoI (25 th %ile,75 th %ile) was 56% (50,87) for low TF and 100% (100,100) for high TF. PPV for CGoI did not differ by TF (p=0.20). High TF was associated with higher levels of TMB and bTMB (p&lt;0.01 for both). TMB LC (CI) for low and high TF were 0.46 (0.27,0.61) and 0.69 (0.53,0.81). Conclusions: High TF was associated with worse OS, better PPA among CGoI, and better LC for t/bTMB. TF may improve the clinical utility of mutations detected by liquid biopsies and should be reported and considered in interpreting these results. [Table: see text]